Over 150,000 soldiers are currently deployed in Iraq as part of Operation Iraqi Freedom (OIF), and 12% of returning OIF soldiers have posttraumatic stress disorder (PTSD). 389,100 soldiers developed chronic PTSD from the Vietnam War, requiring a life-time of mental health care, with a loss of work productivity and greater utilization of health care resources. Research from our group and others showed changes in a functional circuit including hippocampus, medial prefrontal cortex, and amygdala. However these studies used global measures of brain function and structure; little is known about specific neurochemical systems in the brain that mediate PTSD symptoms. The benzodiazepine system mediates an inhibitory effect on brain function. Studies in animals show that stress results in a decrease in benzodiazepine receptor binding in the hippocampus and medial prefrontal cortex. In the only published neuroreceptor study in PTSD to our knowledge we showed a decrease in benzodiazepine receptor binding in medial prefrontal cortex with single photon emission computed tomography (SPECT) in veterans with chronic combat-related PTSD. We now have much higher resolution imaging (2 mm versus 13 mm with SPECT) with a grant funded by the NCRR to the PI for a High Resolution Research Tomograph (HRRT), which has been in place for two years. We have scanned several patients using PET HRRT and [C-11]flumazenil, a neuroreceptor compound that binds to the benzodiazepine receptor and can be used to image benzodiazepine receptor binding in the living human brain. Studies of the neurobiology of PTSD have been primarily performed in patients with long standing and chronic PTSD. There is currently a consensus that early phases of PTSD are different than chronic and long-standing PTSD, and that early interventions before the disorder becomes chronic and unremitting may offer a better opportunity for treatment. The PI is working in the Operation Iraqi Freedom (OIF) Trauma Program at the Atlanta VA, and there over 1000 soldiers returning to the state of Georgia each month, so there are ample sources of recruitment for research on early PTSD. This is a pilot study to measure benzodiazepine receptor binding in returning OIF veterans with and without PTSD, and non combat exposed comparison subjects with PET HRRT [C-11]flumazenil in OIF combat veterans with and without PTSD and non-combat exposed subjects. We hypothesize decreased benzodiazepine receptor binding in the prefrontal cortex in PTSD compared to the other two groups. We will also assess the ability of benzodiazepine binding to predict long-term outcome. We predict decreased prefrontal binding will be associated with progression to chronic PTSD at one year post assessment. Secondary aims are to assess the relationship between PTSD symptoms and benzodiazepine binding in the prefrontal cortex. This project is designed to examine binding of the benzodiazepine receptor in Iraq combat veterans with posttraumatic stress disorder (PTSD) and to see if this measure can be used to predict which returning veterans will progress to the development of chronic PTSD. The benzodiazepine system plays an important role in the regulation of anxiety. Understanding changes in the benzodiazepine system may lead to new treatments for Iraq combat veterans with PTSD; this project also proposes a novel method of testing whether brain imaging can be used to predict outcomes, which could provide an important tool for identifying veterans in need of early intervention. [unreadable] [unreadable] [unreadable]